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Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action.

Abstract

BACKGROUND AND PURPOSE

Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception.

EXPERIMENTAL APPROACH

Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey.

KEY RESULTS

Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB(1) adenosine A(1) and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD.

CONCLUSIONS AND IMPLICATIONS

CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action.

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  • Authors+Show Affiliations

    ,

    Endocannabinoid Research Group, Department of Experimental Medicine - Division of Pharmacology 'L. Donatelli', Second University of Naples, Naples, Italy.

    , , , , , ,

    Source

    British journal of pharmacology 162:3 2011 Feb pg 584-96

    MeSH

    Analgesics
    Anesthesia
    Animals
    Cannabidiol
    Cannabinoid Receptor Modulators
    Cannabinoids
    Male
    Medulla Oblongata
    Microinjections
    Nociceptors
    Pain Measurement
    Periaqueductal Gray
    Rats
    Rats, Wistar
    Receptor, Cannabinoid, CB1
    Signal Transduction
    TRPV Cation Channels
    Tail
    Transient Receptor Potential Channels

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    20942863

    Citation

    TY - JOUR T1 - Non-psychoactive cannabinoids modulate the descending pathway of antinociception in anaesthetized rats through several mechanisms of action. AU - Maione,Sabatino, AU - Piscitelli,Fabiana, AU - Gatta,Luisa, AU - Vita,Daniela, AU - De Petrocellis,Luciano, AU - Palazzo,Enza, AU - de Novellis,Vito, AU - Di Marzo,Vincenzo, PY - 2010/10/15/entrez PY - 2010/10/15/pubmed PY - 2011/7/27/medline SP - 584 EP - 96 JF - British journal of pharmacology JO - Br. J. Pharmacol. VL - 162 IS - 3 N2 - BACKGROUND AND PURPOSE: Two non-psychoactive cannabinoids, cannabidiol (CBD) and cannabichromene (CBC), are known to modulate in vitro the activity of proteins involved in nociceptive mechanisms, including transient receptor potential (TRP) channels of vanilloid type-1 (TRPV1) and of ankyrin type-1 (TRPA1), the equilibrative nucleoside transporter and proteins facilitating endocannabinoid inactivation. Here we have tested these two cannabinoids on the activity of the descending pathway of antinociception. EXPERIMENTAL APPROACH: Electrical activity of ON and OFF neurons of the rostral ventromedial medulla in anaesthetized rats was recorded extracellularly and tail flick latencies to thermal stimuli were measured. CBD or CBC along with various antagonists were injected into the ventrolateral periaqueductal grey. KEY RESULTS: Cannabidiol and CBC dose-dependently reduced the ongoing activity of ON and OFF neurons in anaesthetized rats, whilst inducing antinociceptive responses in the tail flick-test. These effects were maximal with 3 nmol CBD and 6 nmol CBC, and were antagonized by selective antagonists of cannabinoid CB(1) adenosine A(1) and TRPA1, but not of TRPV1, receptors. Both CBC and CBD also significantly elevated endocannabinoid levels in the ventrolateral periaqueductal grey. A specific agonist at TRPA1 channels and a synthetic inhibitor of endocannabinoid cellular reuptake exerted effects similar to those of CBC and CBD. CONCLUSIONS AND IMPLICATIONS: CBD and CBC stimulated descending pathways of antinociception and caused analgesia by interacting with several target proteins involved in nociceptive control. These compounds might represent useful therapeutic agents with multiple mechanisms of action. SN - 1476-5381 UR - https://www.unboundmedicine.com/medline/citation/20942863/abstract/Non_psychoactive_cannabinoids_modulate_the_descending_pathway_of_antinociception_in_anaesthetized_rats_through_several_mechanisms_of_action_ L2 - http://dx.doi.org/10.1111/j.1476-5381.2010.01063.x ER -